Is RECQL4 p.Pro103Ala (c.307C>G) pathogenic?

RECQL4 p.Pro103Ala (c.307C>G) is classified Uncertain significance in RECQL4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-08). AlphaMissense: likely benign (0.0635); Very rare (popmax 0.000424%, nfe); Associated with Baller-Gerold syndrome.

What condition is associated with RECQL4 p.Pro103Ala (c.307C>G)?

RECQL4 p.Pro103Ala (c.307C>G) is associated with Baller-Gerold syndrome (ClinVar).

How common is RECQL4 p.Pro103Ala (c.307C>G) in the general population?

RECQL4 p.Pro103Ala (c.307C>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about RECQL4 p.Pro103Ala (c.307C>G)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

RECQL4 p.Pro103Ala

c.307C>G · rs587778650 · VCV998401

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Baller-Gerold syndrome

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
SaProt	LLR -6.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.5, phastCons 0.97
Regional constraint	o/e 1.39	unconstrained · MANE · 6,350 bp · p 1.8e-56 · regional, not allelic
Overall
CADD	15.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,746 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,442 alleles · very rare exomes 5/1,460,050 · genomes 0/152,392 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RECQL4
Protein: p.Pro103Ala
Coding: c.307C>G
MANE Select: NM_004260
dbSNP: rs587778650
Type: single nucleotide variant
Location: chr8:144517097 (GRCh38)
Gene constraint: LOEUF 1.519 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32 · 2 PDB
Residue 103: a UniProt-annotated variant site (in); the 'disordered' region

Full RECQL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Baller-Gerold syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RECQL4 p.Pro103Ser Uncertain significance ★★ ⚠ same residue
RECQL4 p.Pro103Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RECQL4 p.Pro103= Likely benign ★ same residue
RECQL4 c.1132-1G>A Likely pathogenic ★★ same condition
RECQL4 c.1259-1G>A Pathogenic/Likely pathogenic ★★ same condition
RECQL4 c.1391-1G>A Pathogenic ★★ same condition
RECQL4 c.1704+1G>A Pathogenic/Likely pathogenic ★★ same condition
RECQL4 c.1704+2T>G Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/recql4-p-pro103ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown